Human pathogenic viruses are a kind of nucleic acid particles with very simple structure. Most of them lack enzymatic system, and have to depend on the host cells to replicate their nucleic acids and proteins and then assemble into virus particles so as to realize the multiplication of the viruses. Viral infection can cause various diseases and harm the health and lives of human severely. With the undercount, about 60% epidemical diseases are caused by viral infection. Up to now, more than 3000 kinds of viruses have been found all over the world, and new viruses are being continuously found. At the World Virology Convention held in Paris in August 2002, the 7th report of International Committee on the Taxonomy of Viruses embodies more than 3600 kinds of viruses, in which more than 1200 kinds of viruses are pathogenic to human and can be divided into 29 families, 7 subfamilies and 53 genera. At present, the viruses with high morbidity and great harmfulness mainly include influenza virus, hepatitis B virus, AIDS virus, cytomegalovirus and herpes virus, etc.
Now there still lacks of drugs with high specificity in the treatment of viral diseases, and also the commonly used drugs in clinical therapy mainly are divided into the following types: the antiviral drugs for inhibiting viral replication; the immunomodulators for enhancing the body's immune function; the antitussive, anodyne, antipyretic and antiphlogistic and the like against clinical symptoms; the anti-infection drugs for preventing secondary infection; the vaccines for preventing viral infection and the disinfectants for blocking the transmission of viruses, etc.
The study of new drugs for treating viral diseases abroad focuses on the antiviral drugs. At present, the anti-influenza virus drugs include the adamantine amine drugs, the neuraminidase inhibitors of influenza virus, the receptor blocking agent of influenza virus and the antisense oligonucleotide against influenza virus etc. And the ones used in clinical therapy mainly are the adamantanamine drugs and the neuraminidase inhibitors. However, the hepatitis virus infection is a well-known difficulty in therapeutics so far. More than 80% of the acute infection of the hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) will convert into chronic infection, in which 20% persistent infection may develop to hepatic cirrhosis, and 1% to 5% will change to hepatoma carcinoma. The world health organization has classified hepatitis as the 9th cause of death. China is a region with high incidence of viral hepatitis, and the carriers of hepatitis B virus are more than 120 million. It is estimated that the direct economic loss resulted from viral hepatitis is 30 billion to 50 billion RMB. Therefore, it is a main task for the medical and pharmaceutical domestic and abroad scientists to explore and develop antiviral drugs. The vidarabine, vidarabine phosphate, acyclovir, zidovudine studied in 1980's are not used to treat hepatitis B now abroad due to their poor therapeutic effect and strong toxic adverse effect. In recent years, many large-scale enterprises developed various nucleoside drugs having obvious inhibitory effect to HBV, such as lamivudine, famciclovir, lobucavir, adefovir dipivoxiil, FTC (dideoxyfluorinethiocytosine), FMAU (fluoro-methylarabinosyluracil), FDDC (fluoro-dideocytosine), BMS 200475 (epoxyhydroxylcarbodeoxy guanosine), by using the established hepatoma carcinoma cell lines, hepatitis virus transfected cell lines or transgenic cell lines, and transgenic mouse hepatitis animal model to screen the drugs against hepatitis B virus and hepatitis C virus. The researchers abroad carried out the preclinical research on more than 30 kinds of drugs in 1998-2002. And recently there are 21 drugs entering stage II-III clinical trial, and among them, the trial medicaments for anti-hepatitis B virus are mostly derived from the HIV revertase inhibitor and herpes virus DNA polymerase inhibitor, in which enticavir has been authorized to be commercially available in 2005. Most of the trail medicaments for anti-hepatitis C virus are derived from broad-spectrum antiviral drugs or RNA virus inhibitors and the immunomodulators having antiviral activity.
At present, most of the authorized antivirus drugs are nucleoside compounds. During the clinical uses, they have the following disadvantages: 1) cytotoxicity; 2) occurrence of drug resistant viruses variants induced by long-term medication and the requirement of the other drugs having different structure to antagonize these variants. Therefore, developing non-nucleoside antiviral drugs becomes an arresting aspect.